Stem cell therapy is now being used to treat a plethora of diseases including leukemia, spinal cord injuries, heart diseases, Parkinson's, Alzheimer's, diabetes and arthritis. Since stem cells are capable of self-renewal and differentiation into a variety of mature cell lineages, transplantation of such cells can be utilized as a clinical tool for reconstituting a target tissue, thereby restoring physiologic and anatomic functionality.
In recent years, thermosensitive injectable hydrogels have attracted a great deal of interest in medical applications since they have a great advantage over conventional implantation surgery as they minimize the invasiveness of the implant procedures. Other advantages include easy handling by clinic personnel, reduced pain, less complications, reduced healing period, minimal scarring, reduced surgery time, and the ability to conform to irregular defects.
Among a number of injectable hydrogel candidates, chitosan (CS), a polysaccharide consisting of β-(1,4)-linked glucosamine units, was widely experimented as a biomaterial. It is known that CS is extracted from fungal cell walls and exoskeletons of arthropods such as crabs, shrimp and krill. It holds several characteristics desirable for biomedical applications, such as; biocompatibility, biodegradation, bioadhesivity, anti-bacterial effects and no toxicity. Given the mentioned properties, CS is an ideal material to be used in biomedical applications where the material will be in contact with the patient for prolonged periods. CS and its derivatives have been widely investigated for applications such as; controlled drug and protein release, non-viral gene delivery and tissue engineering. Many studies elaborated its biocompatibility, solubility, pH sensitivity and thermo-sensitivity by grafting different subgroups to the CS backbone, this in order to impart desired biofunctionality to the resulting hydrogel. To achieve chitosan solutions with thermo-induced gelling, CS is typically mixed with polyol salts such as; disodium-, ammonium hydrogen-, glycerol-, sorbitol-, fructose- or glucose-phosphate salts. These salts form ideal agents for transforming purely pH-dependent chitosan solutions into temperature-controlled pH-dependent chitosan solutions. Such solutions are typically liquids at low temperatures, but form gels at elevated temperatures. This makes them suitable as injectable in vivo gelling systems. After injection, due to the elevated temperature of the host, a gel is formed through temperature induced formation of a connective network, in which co-injected therapeutics are embedded, allowing for subsequent pre-designed medical function.